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International Journal of Molecular... Apr 2023The efficacy and the safety of psoriasis medications have been proved in trials, but unideal responses and side effects are noted in clinical practice. Genetic... (Review)
Review
The efficacy and the safety of psoriasis medications have been proved in trials, but unideal responses and side effects are noted in clinical practice. Genetic predisposition is known to contribute to the pathogenesis of psoriasis. Hence, pharmacogenomics gives the hint of predictive treatment response individually. This review highlights the current pharmacogenetic and pharmacogenomic studies of medical therapy in psoriasis. HLA-Cw*06 status remains the most promising predictive treatment response in certain drugs. Numerous genetic variants (such as ABC transporter, DNMT3b, MTHFR, ANKLE1, IL-12B, IL-23R, MALT1, CDKAL1, IL17RA, IL1B, LY96, TLR2, etc.) are also found to be associated with treatment response for methotrexate, cyclosporin, acitretin, anti-TNF, anti-IL-12/23, anti-IL-17, anti-PDE4 agents, and topical therapy. Due to the high throughput sequencing technologies and the dramatic increase in sequencing cost, pharmacogenomic tests prior to treatment by whole exome sequencing or whole genome sequencing may be applied in clinical in the future. Further investigations are necessary to manifest potential genetic markers for psoriasis treatments.
Topics: Humans; Pharmacogenetics; Tumor Necrosis Factor Inhibitors; Psoriasis; Methotrexate; Acitretin; Endonucleases
PubMed: 37108492
DOI: 10.3390/ijms24087329 -
Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss,... (Review)
Review
Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss, disturbance in behavior and personality, and difficulties in learning. Although the main causes of AD pathogenesis are not fully understood yet, amyloid-β peptides and tau proteins are supposed to be responsible for AD onset and pathogenesis. Various demographic, genetic, and environmental risk factors are involved in AD onset and pathogenesis such as age, gender, several genes, lipids, malnutrition, and poor diet. Significant changes were observed in microRNA (miRNA) levels between normal and AD cases giving hope for a diagnostic procedure for AD through a simple blood test. As yet, only two classes of AD therapeutic drugs are approved by FDA. They are classified as acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists (NMDA). Unfortunately, they can only treat the symptoms but cannot cure AD or stop its progression. New therapeutic approaches were developed for AD treatment including acitretin due to its ability to cross blood-brain barrier in the brain of rats and mice and induce the expression of ADAM 10 gene, the α-secretase of human amyloid-β protein precursor, stimulating the non-amyloidogenic pathway for amyloid-β protein precursor processing resulting in amyloid-β reduction. Also stem cells may have a crucial role in AD treatment as they can improve cognitive functions and memory in AD rats through regeneration of damaged neurons. This review spotlights on promising diagnostic techniques such as miRNAs and therapeutic approaches such as acitretin and/or stem cells keeping in consideration AD pathogenesis, stages, symptoms, and risk factors.
Topics: Animals; Humans; Acitretin; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; MicroRNAs; Stem Cell Transplantation; Stem Cells; Disease Susceptibility
PubMed: 37212107
DOI: 10.3233/JAD-221298 -
Clinical and Experimental Dermatology Dec 2022For disorders of keratinization, topical treatment alone may be ineffective, and systemic retinoid therapy may be indicated. Treatment with systemic retinoids...
For disorders of keratinization, topical treatment alone may be ineffective, and systemic retinoid therapy may be indicated. Treatment with systemic retinoids (acitretin, isotretinoin and alitretinoin) has been shown to be effective in reducing disease severity; however, potentially rare adverse effects (AEs) may occur, including hyperostotic skeletal changes. The true prevalence of this AE in adult patients administered life-long therapy is unknown. We identified 3 of 127 (2.4%) patients (with ichthyosis or Darier disease) who had been prescribed isotretinoin with or without acitretin, and who developed radiological signs and clinical symptoms of hyperostosis and ligamentous ossification. This clinical review highlights the significance of retinoid-induced skeletal hyperostosis in patients prescribed long-term, high-dose retinoid therapy for disorders of keratinization. Patients commencing systemic retinoid therapy, particularly women of childbearing age, should be counselled about this important and potentially serious AE, especially if long-term treatment is indicated.
Topics: Adult; Humans; Female; Acitretin; Isotretinoin; Alitretinoin; Hyperostosis; Ichthyosis
PubMed: 35988035
DOI: 10.1111/ced.15382 -
Postepy Dermatologii I Alergologii Jun 2022Psoriasis is a genetic chronic disease mediated by the immune system with systemic and cutaneous manifestations that can significantly deteriorate patients' quality of... (Review)
Review
Psoriasis is a genetic chronic disease mediated by the immune system with systemic and cutaneous manifestations that can significantly deteriorate patients' quality of life. Two-three percent of the population worldwide suffer from psoriasis and it imposes a substantial economic burden on patients. The aetiology is mainly related with genes and environmental factors. The pathophysiology of psoriasis is characterized by T cells and dendritic cells, antimicrobial peptides, genetic predispositions, lipoprotein-2, galactosin-3, fractalkine, vaspin, and human neutrophilic peptides, etc. in the progression of psoriasis. For patients with psoriasis, the traditional treatments include corticosteroids, vitamin D analogues, calcineurin inhibitors, methotrexate, cyclosporine, acitretin, phototherapy, and biological agents, etc. Nanodermatology is an emerging, multidisciplinary science that is gaining increasing recognition in the treatment of psoriasis. This review provides a summary of the pathophysiology, epidemiology, clinical diagnosis, and classical pharmacotherapy of psoriasis. The review also summarizes different nanotechnology therapies for effective treatment of psoriasis.
PubMed: 35950130
DOI: 10.5114/ada.2021.108445 -
Postepy Dermatologii I Alergologii Feb 2022Acitretin, a synthetic analogue of vitamin A is widely used in dermatology. It has an important role in the treatment of psoriasis and keratinization disorders. In... (Review)
Review
Acitretin, a synthetic analogue of vitamin A is widely used in dermatology. It has an important role in the treatment of psoriasis and keratinization disorders. In adults its safety and efficacy has been proven in many studies, but there are some concerns regarding the use of acitretin in paediatric population, especially in high doses and as a long-term therapy. In this article we present the main indications of acitretin in children as well as the positive and negative aspects of acitretin treatment in this age population.
PubMed: 35369612
DOI: 10.5114/ada.2020.98558 -
Psoriasis (Auckland, N.Z.) 2022Although innovative targeted therapies have positively revolutionized psoriasis treatment shifting treatment goals to complete or almost complete skin clearance, primary... (Review)
Review
Although innovative targeted therapies have positively revolutionized psoriasis treatment shifting treatment goals to complete or almost complete skin clearance, primary or secondary lack of efficacy is still possible. Hence, identifying robust biomarkers that reflect the various clinical psoriasis phenotypes would allow stratify patients in subgroups or endotypes, and tailor treatments according to the characteristics of each individual (precision medicine). To sum up the current progress in personalized medicine for psoriasis, we performed a review on the available evidence on biomarkers predictive of response to psoriasis treatments, with focus on phototherapy and systemic agents. Relevant literature published in English was searched for using the following databases from the last five years up to March 20, 2022: PubMed, Embase, Google Scholar, EBSCO, MEDLINE, and the Cochrane library. Currently, more evidence exists towards biologicals, as justified by the huge health care costs as compared to phototherapy or conventional systemic drugs. Among them, most of the studies focused on anti-TNF and IL12/23, with still few on IL17 (mainly secukinumab). The most discussed biomarker gene is the HLA-C*02:06 status that has been shown to be associated with psoriasis, and also differential response to biologicals. Although its positivity is associated with great response to MTX, debatable results were retrieved concerning both anti-TNF and IL12/23 while it seems not to affect secukinumab response. Personalized treatment in psoriasis would provide excellent outcome minimizing the risk of side effects. To date, although several candidates were proposed and assessed, the scarcity and heterogeneity of the results do not allow the identification of the gold-standard biomarker per each treatment. Anyway, the creation of a more comprehensive panel would be more reliable for the treatment decision process.
PubMed: 36071793
DOI: 10.2147/PTT.S328460 -
The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
Drugs Apr 2020Erythrodermic psoriasis (EP) is an extreme and often refractory variant of psoriasis with high morbidity and increased mortality, and is frequently classified as a... (Review)
Review
Erythrodermic psoriasis (EP) is an extreme and often refractory variant of psoriasis with high morbidity and increased mortality, and is frequently classified as a dermatological emergency. The pathophysiology of EP is largely unknown but is thought to differ from that of plaque psoriasis. Treatment of EP is challenging, and usually based on clinical experience and patient co-morbidities, due to its low incidence and limited clinical evidence. Conventional treatments, such as topical glucocorticoid therapy, cyclosporin, acitretin, and methotrexate have some but limited efficacy in EP, and treatment discontinuation may result in flares. Newer biological drugs, including anti-TNF, anti-IL-17, and anti-IL-12/23 agents, have shown promise in therapeutic management of EP, but most of the available evidence is currently based on small case series and reports. Few studies have compared available treatment options for EP, and further clinical studies are necessary to provide clinical data and optimal treatment guidelines for EP patients. Here, we provide a comprehensive review of the background of EP, assess the available clinical data on the efficacy of targeted therapies, and aim to provide a foundation for clinical decision making for this rare form of psoriasis.
Topics: Dermatitis, Exfoliative; Dermatologic Agents; Humans; Psoriasis
PubMed: 32180204
DOI: 10.1007/s40265-020-01283-2 -
Farmacia Hospitalaria : Organo Oficial... 2023The objective of this review is to gather the available evidence on the different drugs used in immune-mediated inflammatory diseases in pregnancy, lactation, their... (Review)
Review
OBJECTIVE
The objective of this review is to gather the available evidence on the different drugs used in immune-mediated inflammatory diseases in pregnancy, lactation, their influence on female and male fertility, advice on discontinuation before conception and to help in routine clinical practice for better patient advice on family planning.
METHODS
A bibliographic search was carried out, where published articles (review studies, observational studies and case series) in English or Spanish until April 2020 that analyzed the management of pregnancy, lactation and/or fertility in patients on treatment in immune-mediated diseases were selected.
RESULTS
A total of 95 references were selected and the information on each drug was synthesized in tables. Drugs contraindicated in pregnancy are topical retinoids, pimecrolimus, cyclooxygenase 2 inhibitors, methotrexate, mycophenolate mofetil, leflunomide, acitretin, and thiopurines. The lack of data advises against the use of apremilast, tofacitinib, baricitinib, anakinra, abatacept, tocilizumab and the new biologicals. Topical salicylates, paracetamol, ultraviolet therapy and hydroxychloroquine treatment are safe, and anti-TNF biological therapy are considered low risk, with certolizumab being the drug of choice throughout pregnancy and lactation. Most are compatible with paternal exposure except for sulfasalazine, mycophenolate and leflunomide, for which suspension of treatment prior to conception is recommended, and cyclosporine with dose requirements of less than 2 mg/kg/day.
CONCLUSIONS
In this context of chronic treatments with teratogenic potential, it is necessary to highlight the importance of pregnancy planning to select the safest drug. Given the quality of the available data, it is still necessary to continuously update the information, as well as to promote observational studies of cohorts of pregnant patients and men of childbearing age, including prospective studies, in order to generate more scientific evidence.
Topics: Pregnancy; Humans; Male; Female; Antirheumatic Agents; Breast Feeding; Leflunomide; Prospective Studies; Tumor Necrosis Factor Inhibitors; Immunosuppressive Agents; Fertility
PubMed: 36732114
DOI: 10.1016/j.farma.2022.12.016 -
International Journal of Women's... Jul 2019The burden of psoriasis is particularly high for women, who report lower levels of happiness (women: 18.5%; men: 11.3% lower vs. general population) and are more likely... (Review)
Review
The burden of psoriasis is particularly high for women, who report lower levels of happiness (women: 18.5%; men: 11.3% lower vs. general population) and are more likely to experience stress (women: > 60%; men: 42%), loneliness (women: 25-28%; men: 19-24%), stigmatization (Feelings of Stigmatization Questionnaire score; women: 93.2; men: 78.0), and reduced sexual activity (women: 33%; men: 19%) compared with men. The onset of psoriasis is bimodal, with one incidence peak (15-30 years) that coincides with the prime reproductive age for women, which poses specific challenges for their treatment. However, well-established guidelines for the treatment of women of childbearing age are lacking. Many women experience stabilization (21%) or improvement (55%) of their skin during pregnancy, but up to a quarter can experience disease worsening, and postpartum flares are common (> 50%). Therefore, balancing the risk of treatment with the risk of uncontrolled disease is important. Because half of pregnancies are unplanned, the implications of therapeutic options must be considered for all women with psoriasis who are sexually active, irrespective of intentions to start a family. Timely initiation of these discussions by health care professionals is paramount to prevent unintentional toxicity to the developing fetus. For example, acitretin, methotrexate, and oral psoralen/ultraviolet A are all contraindicated in pregnancy. Reassuringly, safety data for other psoriasis treatments during pregnancy are increasingly available, particularly for anti-tumor necrosis factor therapies. Despite encouraging data from pregnancy exposure registries and clinical studies now being included in anti-tumor necrosis factor drug labels, comfort with prescribing these therapies to pregnant women remains low (U.S. dermatologists: 21%; EU-5 dermatologists: 10%). In this article, we review issues specific to treating women of childbearing age with psoriasis and highlight the need for treatment guidelines to ensure consistent care and optimal outcomes for these patients.
PubMed: 31360745
DOI: 10.1016/j.ijwd.2019.04.021